Evidence from several studies has suggested that amounts of DHA and EPA in the form of fish or fish oil supplements lowers triglycerides, slows the buildup of atherosclerotic plaques ("hardening of the arteries"), lowers blood pressure slightly, as well as reduces the risk of death, heart attack, dangerous abnormal heart rhythms, and strokes in people with known heart disease. However, high doses may have harmful effects, such as an increased risk of bleeding. Although similar benefits are proposed for alpha-linolenic acid, scientific evidence is less compelling, and beneficial effects may be less pronounced.

Some species of fish carry a higher risk of environmental contamination, such as with methylmercury.

Evidence

DISCLAIMER:
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

High blood pressure:
Multiple human trials report small reductions in blood pressure with intake of omega-3 fatty acid. DHA may have greater benefits than EPA. However, it may be necessary to take high amounts of omega-3 fatty acids per day to obtain these health benefits, and high doses may increase the risk of bleeding. Therefore, a qualified healthcare provider should be consulted before starting treatment with fish oil supplements.
Grade: A

Secondary cardiovascular disease prevention (fish oil / EPA plus DHA):
Several studies report that regular consumption of oily fish or fish oil/omega-3 supplements reduces the risk of non-fatal heart attacks, fatal heart attacks, sudden death, and deaths due to any cause in people with histories of heart attacks. Most patients in these studies were also using standard heart drugs, suggesting that the benefits of fish oils may add to the effects of other therapies.
Grade: A

Infant eye / brain development:
Early evidence suggests that infants have improved problem solving skills but not memory if their mothers consume DHA-containing functional foods during pregnancy. Other research suggests that DHA supplementation during pregnancy plays an important role in the development of the visual system.
Grade: B

Inflammation:
Research has shown that omega-3 fatty acids help reduce inflammation. Scientists believe that their anti-inflammatory effects may help protect against heart disease.
Grade: B

Nutrition (in gastrointestinal disorders):
Early evidence suggests that omega-3 fatty acid supplements may be a good source of nutrition for patients with Crohn's disease or for those who need to be tube fed after abdominal surgeries.
Grade: B

Pregnancy nutritional supplement:
DHA has been found to be important for healthy pregnancies. Research shows that fish oil supplementation from the 22nd week of pregnancy until delivery improves the amount of n-3 LC-PUFA in the fetus and the mother.
Grade: B

Primary cardiovascular disease prevention (fish intake):
Several large studies of populations (called epidemiological studies) report a significantly lower rate of death from heart disease in people who regularly eat fish. Other epidemiological research reports no such benefits. It is unclear if benefits only occur in certain groups of people, such as those at risk of developing heart disease. Fish oil is also associated with improved blood vessel functioning and decreased resting heart rate. Overall, the evidence suggests benefits of regular consumption of fish oil.
Grade: B

Protection from cyclosporine toxicity in organ transplant patients:
There are many studies of heart transplant and kidney transplant patients taking cyclosporine (Neoral®), who received fish oil supplements. Most trials report improvements in kidney function and reduced high blood pressure compared to patients not taking fish oil. Although several recent studies report no benefits for kidney function, the weight of scientific evidence favors the beneficial effects of fish oil.
Grade: B

Rheumatoid arthritis (fish oil):
Many studies report improvements in morning stiffness and joint tenderness with the regular intake of fish oil supplements for up to three months. Fish oil has been shown to increase the effects of anti-inflammatory medications, such as NSAIDs (such as ibuprofen). However, because of weaknesses in study designs and reporting, better research is needed before a strong favorable recommendation can be made.
Grade: B

Age related macular degeneration:
It has been suggested that omega-3 fatty acids may help prevent an eye disorder, called age-related macular degeneration. However, more research is needed to confirm these early findings.
Grade: C

Angina pectoris:
Early studies report reductions in chest pain (called angina) associated with fish oil intake. Better research is necessary before a firm conclusion can be drawn.
Grade: C

Asthma:
Several studies in this area do not provide enough reliable evidence to form a clear conclusion, with some studies reporting no effects, and others finding benefits. Because most studies have been small without clear descriptions of design or results, the results cannot be considered conclusive.
Grade: C

Atherosclerosis:
Some research reports that regular intake of fish or fish oil supplements reduces the risk of developing atherosclerotic plaques in the arteries of the heart, while other research reports no effects. Additional evidence is necessary before a firm conclusion can be drawn in this area.
Grade: C

Attention deficit hyperactivity disorder (related learning and behavioral problems):
There is evidence that polyunsaturated fatty acids (PUFAs) may help treat ADHD-related problems, including inattention, hyperactivity, and impulsivity. More research is needed to confirm these findings.
Grade: C

Bipolar disorder:
It is unclear if omega-3 fatty acids can help improve symptoms of bipolar disorder. Study results are mixed.
Grade: C

Cancer prevention:
Several population (epidemiological) studies report that dietary omega-3 fatty acids or fish oil may reduce the risk of developing breast, colon, or prostate cancer. Better-designed studies are necessary before a clear conclusion can be drawn.
Grade: C

Cardiac arrhythmias (abnormal heart rhythms):
There is promising evidence that omega-3 fatty acids may decrease the risk of irregular heartbeats (called cardiac arrhythmias). It is possible that this action may be responsible for reducing the number of heart attacks in people who regularly ingest fish oil or EPA + DHA. In patients with defibrillators, there is emerging evidence that fish oil supplementation may not be safe, and its effectiveness has been questioned. Additional research is needed in this area before a firm conclusion can be reached.
Grade: C

Colon cancer:
Cancer patients have been reported to commonly take omega-3 fatty acids. Early studies report that fish oil may reduce the growth of colon cancer cells and polyps. However, it is unclear if fish oil effects cancer survival or remission.
Grade: C

Coronary disease (acute coronary syndrome):
Because higher levels of omega-3 fatty acids have been shown to reduce the risk of sudden cardiac death, researchers have tested if the same is true for acute coronary syndrome (ACS). Early evidence suggests that people who have low levels of EPA and DHA may have an increased risk of developing ACS. More research is needed in this area.
Grade: C

Cystic fibrosis:
A small amount of research in this area does not provide enough reliable evidence to form a clear conclusion.
Grade: C

Dementia:
Well-designed clinical trials are needed before omega-3 fatty acids can be recommended for the prevention of cognitive impairment or dementia.
Grade: C

Depression:
Low levels of omega-3 fatty acids have been linked to depression. Some studies suggest that supplements may decrease suicidal behavior and improve symptoms of postpartum depression and childhood depression. However, more research is needed to confirm these early findings.
Grade: C

Dysmenorrhea (painful menstruation):
There is early evidence suggesting possible benefits of fish oil/omega-3 fatty acids in women with dysmenorrhea. Additional research is needed before a firm conclusion can be reached.
Grade: C

Eczema:
It is unclear if EPA can help treat eczema. More research is needed.
Grade: C

Energy:
Early evidence suggests that fish oil may not improve energy metabolism or energy efficiency during exercise in healthy adults. More research is needed.
Grade: C

Epilepsy:
In patients with chronic refractory epilepsy, a disorder that causes seizures, omega-3 supplements may improve brain energy metabolism and increase the level of phospholipids in the brain. More research is needed to determine if this is an effective treatment for patients with epilepsy.
Grade: C

Growth rates:
Early research suggests that DHA taken by pregnant and breastfeeding mothers may reduce the body mass index of infants. However, supplements have not been shown to affect the length or head size of infants. More research is needed to understand exactly how omega-3 fatty acids may affect the growth and development of unborn babies and infants.
Grade: C

IgA nephropathy:
There are mixed results from several trials in this area.
Grade: C

Immune function:
Some research suggests that fish oil supplementation during pregnancy may speed up the infant's immune system development. However, it is unclear if this affects the infant's health in the future. Other research suggests that supplements during pregnancy may affect the functioning of white blood cells, called neutrophils. More research is needed to fully understand how fish oil affects the immune system.
Grade: C

Impulse problems:
Early evidence suggests that omega-3 fatty acids may help regulate mood and impulse control. More research is needed in this area.
Grade: C

Inflammatory bowel disease (IBD):
It has been suggested that omega-3 fatty acids may reduce pain and inflammation associated with inflammatory bowel disease (Crohn's disease and ulcerative colitis) when added to standard therapy. However, study results are mixed, and no clear conclusion can be made at this time.
Grade: C

Lupus erythematosus:
There is not enough reliable evidence to form a clear conclusion in this area.
Grade: C

Nephrotic syndrome:
There is not enough reliable evidence to form a clear conclusion in this area.
Grade: C

Osteoporosis:
Early evidence suggests that plant sources of dietary n-3 PUFA may help protect against bone loss. More research is needed to confirm these findings.
Grade: C

Peripheral vascular disease / claudication:
Peripheral vascular disease (PVD) occurs when the blood vessels to the arms and legs are clogged. When the muscles do not get enough blood, it causes a type of pain, called claudication. Some evidence suggests that fish oil may improve blood pressure in the legs of patients with PVD and increase how far they can walk until they feel pain. More research is needed.
Grade: C

Phenylketonuria (PKU):
Patients with PKU must follow a diet that does not contain any phenylalanine, which is found in high-protein foods, such as cheese, milk, nuts, or meats. Therefore, low levels of AA and DHA are common among children with PKU during the first year of life. Early research suggests that long chain polyunsaturated fatty acid (LCPUFA) supplementation of PKU diets during the first year of life improves LCPUFA levels so that they are similar to those of healthy, breastfed infants.
Grade: C

Preeclampsia:
If is unclear if fish oil helps treat or prevent preeclampsia in pregnant women. More research is needed.
Grade: C

Primary cardiovascular disease prevention (α-linolenic acid [ALA]):
Additional research is necessary before a conclusion can be drawn in this area.
Grade: C

Prostate problems:
Early research suggests that walnuts do not affect blood levels of prostate-specific antigen (PSA). PSA is a marker of prostate enlargement, inflammation, and cancer.
Grade: C

Psoriasis:
Several studies in this area do not provide enough reliable evidence to form a clear conclusion.
Grade: C

Schizophrenia:
Early evidence suggests that omega-3 fatty acids may help improve symptoms of schizophrenia. Evidence suggests that a combination of omega-3 fatty acids and antioxidants might also reduce the side effects of haloperidol, an antipsychotic medication.
Grade: C

Secondary cardiovascular disease prevention (α-linolenic acid [ALA]):
Several randomized controlled trials have examined the effects of alpha-linolenic acid in people with histories of heart attacks. Although some studies suggest benefits, others do not. Additional research is needed before a conclusion can be drawn in this area.
Grade: C

Stroke prevention:
Several large studies of populations (called epidemiological studies) have tested the effects of omega-3 fatty acid intake on stroke risk. Some studies suggest benefits, while others do not. Effects are likely on ischemic or thrombotic stroke risk, and very large intakes of omega-3 fatty acids ("Eskimo" amounts) may actually increase the risk of hemorrhagic (bleeding) stroke. At this time, it is unclear if there are benefits in people with or without histories of strokes or if effects of fish oil are similar to other treatment strategies.
Grade: C

Appetite / weight loss in cancer patients:
There is early evidence that fish oil supplementation does not improve appetite or prevent weight loss in cancer patients. Further study is needed.
Grade: D

Diabetes:
The available scientific evidence suggests that there are no significant long-term effects of fish oil in patients with diabetes. Most studies in this area are not well designed.
Grade: D

Hypercholesterolemia:
Although fish oil is able to reduce triglycerides, beneficial effects on blood cholesterol levels have not been demonstrated. Fish oil supplements appear to cause small improvements in high-density lipoprotein ("good cholesterol"); however, increases (worsening) in low-density lipoprotein levels ("bad cholesterol") are also observed. Fish oil does not appear to affect C-reactive protein (CRP) levels.
Grade: D

Transplant rejection prevention (kidney and heart):
There are many studies of heart transplant and kidney transplant patients taking cyclosporine (Neoral®) who received fish oil supplements. The majority of trials report improvements in kidney function (glomerular filtration rate, serum creatinine) and less hypertension (high blood pressure) compared to patients not taking fish oil. However, several recent studies report no benefits on kidney function, and no changes have been found in rates of rejection or graft survival.
Grade: D

Tradition

WARNING:
DISCLAIMER:
The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.

Dosing

Adults (over 18 years old)

Average Americans consume about 1.6 grams of omega-3 fatty acids each day, of which about 1.4 grams (~90%) comes from α-linolenic acid, and only 0.1-0.2 grams (~10%) from EPA and DHA. In Western diets, people consume roughly 10 times more omega-6 fatty acids than omega-3 fatty acids. These large amounts of omega-6 fatty acids come from the common use of vegetable oils containing linoleic acid (for example: corn oil, evening primrose oil, pumpkin oil, safflower oil, sesame oil, soybean oil, sunflower oil, walnut oil, and wheatgerm oil). Because omega-6 and omega-3 fatty acids compete with each other to be converted to active metabolites in the body, benefits can be reached either by decreasing intake of omega-6 fatty acids or by increasing omega-3 fatty acids.

For healthy adults with no history of heart disease, the American Heart Association recommends eating fish at least twice weekly. In particular, fatty fish are recommended, such as anchovies, bluefish, carp, catfish, halibut, herring, lake trout, mackerel, pompano, salmon, striped sea bass, tuna (albacore), and whitefish. It is also recommended to consume plant-derived sources of α-linolenic acid, such as tofu/soybeans, walnuts, flaxseed oil, and canola oil. The World Health Organization and governmental health agencies of several countries recommend consuming 0.3-0.5 grams of daily EPA + DHA and 0.8-1.1 grams of daily α-linolenic acid. A doctor and pharmacist should be consulted for dosing for other conditions.

Children (under 18 years old)

Omega-3 fatty acids are used in some infant formulas, although effective doses are not clearly established. Ingestion of fresh fish should be limited in young children due to the presence of potentially harmful environmental contaminants. Fish oil capsules should not be used in children except under the direction of a physician.

Safety

DISCLAIMER:
Many complementary techniques are practiced by healthcare professionals with formal training, in accordance with the standards of national organizations. However, this is not universally the case, and adverse effects are possible. Due to limited research, in some cases only limited safety information is available.

Allergies

People with allergy or hypersensitivity to fish should avoid fish oil or omega-3 fatty acid products derived from fish. There have been rare reports of skin rash. People who are allergic or hypersensitive to nuts should avoid alpha linolenic acid or omega-3 fatty acid products that are derived from the types of nuts to which they react.

Side Effects and Warnings

The U.S. Food and Drug Administration (FDA) classifies omega-3 fatty acids from fish as GRAS (Generally Regarded as Safe). Caution may be warranted, however, in diabetic patients due to potential (albeit unlikely) increases in blood sugar levels, patients at risk of bleeding, or in those with high levels of low-density lipoprotein (LDL). Fish meat may contain methylmercury and caution is warranted in young children and pregnant/breastfeeding women.

Omega-3 fatty acids may increase the risk of bleeding, although there is little evidence of significant bleeding risk at lower doses. Very large intakes of fish oil/omega-3 fatty acids ("Eskimo" amounts) may increase the risk of hemorrhagic (bleeding) stroke. High doses have also been associated with nosebleed and blood in the urine. Fish oils appear to decrease platelet aggregation and prolong bleeding time, increase fibrinolysis (breaking down of blood clots), and may reduce von Willebrand factor. Fish oil should be used cautiously in patients with abnormal heart rhythms (ventricular tachycardia).

Potentially harmful contaminants such as dioxins, methylmercury, and polychlorinated biphenyls (PCBs) are found in some species of fish. Methylmercury accumulates in fish meat more than in fish oil, and fish oil supplements appear to contain almost no mercury. Therefore, safety concerns apply to eating fish but likely not to ingesting fish oil supplements. Heavy metals are most harmful in young children and pregnant/nursing women.

Gastrointestinal upset is common with the use of fish oil supplements. Diarrhea may also occur, with potentially severe diarrhea at very high doses. There are also reports of increased burping, acid reflux/heartburn/indigestion, abdominal bloating, and abdominal pain. Fishy aftertaste is a common effect. Gastrointestinal side effects can be minimized if fish oils are taken with meals and if doses are started low and gradually increased.

Multiple human trials report small reductions in blood pressure with intake of omega-3 fatty acids. Reductions of 2-5 millimeters of mercury have been observed, and effects appear to be dose-responsive (higher doses have greater effects). DHA may have greater effects than EPA. Caution is warranted in patients with low blood pressure or in those taking blood-pressure lowering medications.

Fish oil has caused swelling of the nasal passages and the upper part of the pharynx (called nasopharyngitis) in some patients. Some patients taking fish oil developed upper respiratory tract infections.

Although slight increases in fasting blood glucose levels have been noted in patients with type 2 ("adult-onset") diabetes, the available scientific evidence suggests that there are no significant long-term effects of fish oil in patients with diabetes, including no changes in hemoglobin A1c levels. Limited reports in the 1980s of increased insulin needs in diabetic patients taking long-term fish oils may be related to other dietary changes or weight gain.

Fish oil taken for many months may cause a deficiency of vitamin E, and therefore vitamin E is added to many commercial fish oil products. As a result, regular use of vitamin E-enriched products may lead to elevated levels of this fat-soluble vitamin. Fish liver oil contains the fat-soluble vitamins A and D, and therefore fish liver oil products (such as cod liver oil) may increase the risk of vitamin A or D toxicity.

Mild elevations in liver function tests (alanine aminotransferase) and skin rashes have been reported rarely. There are also rare reports of mania in patients with bipolar disorder or major depression. Restlessness and formication (the sensation of ants crawling on the skin) have also been reported.

Pregnancy and Breastfeeding

Potentially harmful contaminants such as dioxins, methylmercury, and polychlorinated biphenyls (PCBs) are found in some species of fish, and may be harmful in pregnant/nursing women. Methylmercury accumulates in fish meat more than in fish oil, and fish oil supplements appear to contain almost no mercury. Therefore, these safety concerns apply to eating fish but likely not to ingesting fish oil supplements. However, unrefined fish oil preparations may contain pesticides.

It is not known if omega-3 fatty acid supplementation of women during pregnancy or breastfeeding is beneficial to infants. It has been suggested that high intake of omega-3 fatty acids during pregnancy, particularly DHA, may increase birth weight and gestational length. However, higher doses may not be advisable due to the potential risk of bleeding. Fatty acids are added to some infant formulas.

Based on human studies, omega-3 fatty acids may lower blood pressure and add to the effects of drugs that may also affect blood pressure.

Fish oil supplements may lower blood sugar levels a small amount. Caution is advised when using medications that may also lower blood sugar. Patients taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare provider. Medication adjustments may be necessary.

Omega-3 fatty acids lower triglyceride levels, but can actually increase (worsen) low-density lipoprotein (LDL/"bad cholesterol") levels by a small amount. Therefore, omega-3 fatty acids may add to the triglyceride-lowering effects of agents like niacin/nicotinic acid, fibrates such as gemfibrozil (Lopid®), or resins such as cholestyramine (Questran®). However, omega-3 fatty acids may work against the LDL-lowering properties of "statin" drugs like atorvastatin (Lipitor®) and lovastatin (Mevacor®).

Interactions with Herbs and Dietary Supplements

In theory, omega-3 fatty acids may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.

Based on human studies, omega-3 fatty acids may lower blood pressure and theoretically may add to the effects of agents that may also affect blood pressure.

Fish oil supplements may lower blood sugar levels a small amount. Caution is advised when using herbs or supplements that may also lower blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.

Omega-3 fatty acids lower triglyceride levels, but can actually increase (worsen) low-density lipoprotein (LDL/"bad cholesterol") levels by a small amount. Therefore, omega-3 fatty acids may add to the triglyceride-lowering effects of agents like niacin/nicotinic acid, but may work against the potential LDL-lowering properties of agents like barley, garlic, guggul, psyllium, soy, or sweet almond.

Fish oil taken for many months may cause a deficiency of vitamin E, and therefore vitamin E is added to many commercial fish oil products. As a result, regular use of vitamin E-enriched products may lead to elevated levels of this fat-soluble vitamin. Fish liver oil contains the fat-soluble vitamins A and D, and therefore fish liver oil products (such as cod liver oil) may increase the risk of vitamin A or D toxicity. Since fat-soluble vitamins can build up in the body and cause toxicity, patients taking multiple vitamins regularly or in high doses should discuss this risk with their healthcare practitioners.

Bibliography

DISCLAIMER:
Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

Almqvist C, Garden F, Xuan W, et al. Omega-3 and omega-6 fatty acid exposure from early life does not affect atopy and asthma at age 5 years. J Allergy Clin Immunol 2007 Jun;119(6):1438-44.

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